Xu Yan, Yu Zhangbin, Li Qianqian, Zhou Jinjun, Yin Xiaoguang, Ma Yuelan, Yin Yujie, Jiang Shanyu, Zhu Rongping, Wu Yue, Han Liangrong, Gao Yan, Xue Mei, Qiao Yu, Zhu Lingling, Tu Wenjuan, Wu Mingfu, Wan Jun, Wang Weiyuan, Deng Xiaoyi, Li Shuangshuang, Wang Sannan, Chen Xiaoqing, Zhou Qin, Wang Jinxiu, Cheng Rui, Wang Jun, Han Shuping
Department of Neonatology, The Affiliated Hospital of Xuzhou Medical University, No. 99, Huaihai West Road, Xuzhou, 221000, Jiangsu Province, China.
Department of Neonatology, The Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, 210004, Jiangsu, China.
BMC Pediatr. 2020 Nov 16;20(1):522. doi: 10.1186/s12887-020-02394-1.
Human milk has potential protective effects against bronchopulmonary dysplasia (BPD). However, studies on the association between the dose of human milk and BPD in China are limited. This study aimed to evaluate the dose-dependent effects of human milk on BPD and other neonatal morbidities in very low birth weight (VLBW) infants.
This retrospective cohort study of preterm infants was conducted on preterm infants of gestational age ≤ 34 weeks and birth weight < 1500 g admitted to the multicenter clinical research database for breastfeeding quality improvement in Jiangsu province. The multivariate analysis was performed to compare the effect outcomes of daily graded doses [1-24 mL/(kg · day), 25-49 mL/(kg · day), and ≥ 50 mL/(kg · day) of body weight] of human milk on neonatal outcomes throughout the first 4 weeks of life versus a reference group receiving no human milk. The models were adjusted for potential confounding variables.
Of 964 included infants, 279 (28.9%) received exclusive preterm formula, 128 (13.3%) received 1-24 ml/(kg · day), 139 (14.4%) received 25-49 ml/(kg · day), and 418 (43.4%) received ≥50 ml/(kg · day) human milk for the first 4 weeks of life. Compared with infants receiving exclusive formula, those receiving the highest volume of human milk daily [≥50 mL/(kg · day)] had lower incidences of BPD [27.5% in ≥50 mL/(kg · day) vs 40.1% in 0 mL/(kg · day) human milk, P = 0.001)], moderate and severe BPD [8.9% in ≥50 mL/(kg · day) vs 16.1% in 0 mL/(kg · day), P = 0.004], necrotizing enterocolitis [NEC; 3.8% in ≥50 mL/(kg · day) vs 10.8% in 0 mL/(kg · day), P = 0.001], late-onset sepsis [LOS; 9.3% in ≥50 mL/(kg · day) vs 19.7% in 0 mL/(kg · day), P <0.01], and extrauterine growth retardation [EUGR; 38.5% in ≥50 mL/(kg · day) vs 57.6% in 0 mL/(kg · day), P <0.01)]. The logistic regression indicated that those receiving ≥50 ml/kg · day human milk had lower odds of BPD [adjusted odds ratio (AOR) 0.453; 95% confidence interval (CI): 0.309, 0.666], moderate and severe BPD (AOR 0.430; 95% CI: 0.249, 0.742), NEC (AOR 0.314; 95% CI: 0.162, 0. 607), LOS (AOR 0.420; 95% CI: 0.263, 0.673), and EUGR (AOR 0.685; 95% CI: 0.479, 0.979).
A daily threshold amount of ≥50 ml/(kg · day) human milk in the first 4 weeks of life was associated with lower incidence of BPD as well as NEC, LOS, and EUGR in VLBW infants.
ClinicalTrials.gov Identifier: NCT03453502 . Registration date: March 5, 2018. This study was retrospectively registered.
母乳对支气管肺发育不良（BPD）具有潜在的保护作用。然而，在中国，关于母乳摄入量与BPD之间关联的研究有限。本研究旨在评估极低出生体重（VLBW）婴儿中母乳对BPD及其他新生儿疾病的剂量依赖性影响。
本回顾性队列研究针对江苏省母乳喂养质量改善多中心临床研究数据库中收治的孕周≤34周、出生体重<1500g的早产儿进行。采用多变量分析比较出生后前4周内不同日分级母乳摄入量[1 - 24mL/（kg·天）、25 - 49mL/（kg·天）和≥50mL/（kg·天）体重]对新生儿结局的影响，并与未摄入母乳的参照组进行对比。模型对潜在混杂变量进行了校正。
964例纳入婴儿中，279例（28.9%）接受纯早产儿配方奶，128例（13.3%）接受1 - 24mL/（kg·天）的母乳，139例（14.4%）接受25 - 49mL/（kg·天）的母乳，418例（43.4%）在出生后前4周接受≥50mL/（kg·天）的母乳。与接受纯配方奶的婴儿相比，每日接受最高量母乳[≥50mL/（kg·天）]的婴儿，BPD发病率较低[≥50mL/（kg·天）组为27.5%，0mL/（kg·天）母乳组为40.1%，P = 0.001]，中重度BPD发病率较低[≥50mL/（kg·天）组为8.9%，0mL/（kg·天）组为16.1%，P = 0.004]，坏死性小肠结肠炎[NEC；≥50mL/（kg·天）组为3.8%，0mL/（kg·天）组为10.8%，P = 0.001]，晚发性败血症[LOS；≥50mL/（kg·天）组为9.3%，0mL/（kg·天）组为19.7%，P<0.01]，宫外生长发育迟缓[EUGR；≥50mL/（kg·天）组为38.5%，0mL/（kg·天）组为57.6%，P<0.01]。逻辑回归分析表明，接受≥50ml/kg·天母乳的婴儿发生BPD的几率较低[校正优势比（AOR）0.453；95%置信区间（CI）：0.309，0.666]，中重度BPD（AOR 0.430；95%CI：0.249，0.742），NEC（AOR 0.314；95%CI：0.162，0.607），LOS（AOR 0.420；95%CI：0.263，0.673）和EUGR（AOR 0.685；95%CI：0.479，0.979）。
出生后前4周内每日母乳摄入量≥50mL/（kg·天）与VLBW婴儿BPD以及NEC、LOS和EUGR的发病率较低相关。
ClinicalTrials.gov标识符：NCT03453502。注册日期：20I8年3月5日。本研究为回顾性注册研究。
